Menkes Kinky Hair Syndrome is an x-linked recessive condition of early infancy characterized by rapidly progressive CNS degeneration associated with a generalized abnormality of copper metabolism. Parenteral copper therapy has not been shown to be of any clinical benefit for the treatment of this condition. An analogous disorder has been described in the x-linked murine mutant brindled, an animal model for Menkes Syndrome. Affected male mice demonstrated early, neurologic disturbances and die within the first 14 days of life. Intestinal absorption of copper is impaired, and serum, liver and brain copper levels are decreased; parenteral copper only partially corrects the chemical abnormalities resulting from impaired copper metabolism. The x-linked murine mutant, pallid, is characterized by multiple abnormalities resulting from defective manganese metabolism, but prenatal manganese supplementation of pregnant dams partially corrects the abnormalities in their offspring. This and the copper cupplementation of pregnant dams of the mutant crinkled, provides a precedent for successful prenatal treatment of diseases of trace metal metabolism. Copper and cadmium metabolism have been shown to be abnormal in cultured Menkes Syndrome fibroblasts. The abnormality in cadmium metabolism implicates an abnormality in metallothionein, however the major copper-binding intracellular protein has been postulated to be copper-chelatin. This project will investigate the effectiveness of prenatal copper supplementation of the brindled mutant. It will also compare the organ distribution of pre-and/or postnatally administered 67Cu between brindled males and normals. Finally, the mice will be copper- and cadmium- loaded pre- and/or postnatally to compare metalloprotein responses of mutant and normal mice. The goals of this project are the investigation of the effectiveness of prenatal treatment in this mutant, and the clarification of the roles of metallothionein and copper-chelatin in copper metabolism.